Treatment of Myasthenia Gravis Based on Its Immunopathogenesis

Kim, Jee Young; Park, Kee Duk; Richman, David P.

doi:10.3988/jcn.2011.7.4.173

Cited by 45 publications

(41 citation statements)

References 58 publications

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“…In experimental animals, hIgG reduces the severity of experimental autoimmune encephalomyelitis by several potential mechanisms, including expansion of a specific regulatory T cell population, neutralization of the pro-inflammatory cytokine TNFα, and inhibition of metalloproteinase activity (Ephrem et al, 2008; Niimi et al, 2011; Weishaupt et al, 2002). Finally, hIgG has also shown efficacy in myasthenia gravis (Kim et al, 2011), an autoimmune disease that sometimes accompanies NMO (Jarius et al, 2012; Leite et al, 2012), in which autoantibodies against acetylcholine receptors (AChRs) at the neuromuscular junction cause complement activation (Kim et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Human immunoglobulin G reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica

Ratelade

Smith

Verkman

2014

Experimental Neurology

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Neuromyelitis optica (NMO) pathogenesis involves binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) present in serum to AQP4 on astrocytes, which causes complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Human immunoglobulin G (hIgG) is effective for treatment of humorally mediated neurological autoimmune diseases and has been reported to improve disease outcome in a limited number of NMO patients. Here, we investigated hIgG actions on NMO-IgG pathogenicity using an in vivo rat model of NMO and in vitro assays. In rats administered NMO-IgG by intracerebral injection, the size of neuroinflammatory demyelinating lesions was reduced by ∼ 50 % when hIgG was administered by intraperitoneal injection to reach levels of 10-25 mg/mL in rat serum, comparable with human therapeutic levels. In vitro, hIgG at 10 mg/mL reduced by 90 % NMO-IgG-mediated CDC following addition of NMO-IgG and human complement to AQP4-expressing cells. The hIgG effect was mainly on the classical complement pathway. hIgG at 10 mg/mL also reduced by up to 90 % NMO-IgG-mediated ADCC as assayed with human natural killer cells as effector cells. However, hIgG at up to 40 mg/mL did not affect AQP4 cell surface expression or its supramolecular assembly in orthogonal arrays of particles, nor did it affect NMO-IgG binding to AQP4. We conclude that hIgG reduces NMO-IgG pathogenicity by inhibition of CDC and ADCC, providing a mechanistic basis to support further clinical evaluation of its therapeutic efficacy in NMO.

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Section: Discussionmentioning

confidence: 99%

Human immunoglobulin G reduces the pathogenicity of aquaporin-4 autoantibodies in neuromyelitis optica

Ratelade

Smith

Verkman

2014

Experimental Neurology

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“…In the present, the prognosis of MG has improved dramatically due to advances in critical care and symptomatic treatment [1]. MG is a B-cell-mediated, T-cell-dependent autoimmune disorder resulting from loss of tolerance toward self-antigens in the thymus.…”

Section: Introductionmentioning

confidence: 99%

Shenqi Fuzheng Injection Alleviates the Transient Worsening Caused by Steroids Pulse Therapy in Treating Myasthenia Gravis

Liu

Gao

2013

Evidence-Based Complementary and Alternative Medicine

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Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy.

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“…Many studies suggest that the earlier the thymectomy is performed in the course of the disease, the better the results of the treatment, especially during the first two years of the disease. The therapeutic effect of thymectomy usually occurs after about one year [39]. The interest and indications of thymectomy in MG are still debated and are still not the subject of a consensus.…”

Section: Discussionmentioning

confidence: 99%